Col1a1-cre mediated activation of β-catenin leads to aberrant dento-alveolar complex formation

Wnt/beta-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/beta-catenin signaling is involved in the dento-alveolar complex formation is unknown. To understand the roles of Wnt/beta-catenin signaling in the dento-alveolar complex formation, we generated conditional beta-catenin activation mice through intercross of Catnb(+/lox(ex3)) mice with Col1a1-cre mice. In mutant mice, tooth formation and eruption was disturbed. Lower incisors and molars did not erupt. Bone formation was increased in the mandible but tooth formation was severely disturbed. Hypomineralized dentin was deposited in the crown but roots of molars were extremely short and distorted. In the odontoblasts of mutant molars, expression of dentin matrix proteins was obviously downregulated following the activation of beta-catenin whereas that of mineralization inhibitor was increased. Cementum and periodontal ligament were hypoplastic but periodontal space was narrow due to increased alveolar bone formation. While cementum matrix proteins were decreased, bone matrix proteins were increased in the cementum and alveolar bone of mutant mice. These results indicate that local activation of beta-catenin in the osteoblasts and odontoblasts leads to aberrant dento-alveolar complex formation. Therefore, appropriate inhibition of Wnt/beta-catenin signaling is important for the dento-alveolar complex formation.